tbuckley/cabot-search huggingface dataset:
P1204: AXICABTAGENE CILOLEUCEL VEIN-TO-VEIN TIME IN TRIAL OR REAL-WORLD SETTINGS VS OTHER CAR T-CELL THERAPIES FOR RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS
Authors: Frederick Locke, Michael T. Hemmer, Steve Kanters, Michael J. Zoratti, Zhen-Huan Hu, Harry Miao, Shilpa Shahani, Clare Spooner, Christine Fu, Anik Patel, Hairong Xu, Marcelo Pasquini
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Autologous chimeric antigen receptor (CAR) T-cell products are manufactured using individual patient cells, leading to variable time between leukapheresis and infusion, or vein-to-vein time (V2Vt). V2Vt compromises sub-intervals, including time for transportation, manufacturing, and quality release. Aims: This systematic literature review and meta-analysis describes the heterogeneous V2Vt for axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) in relapsed or refractory large B-cell lymphoma (r/r LBCL). Methods: Systematic searches of MEDLINE, Embase, CENTRAL, and select conferences were conducted on 5 October 2022. Treatment-specific, non-comparative meta-analyses for each pre–CAR T-cell infusion time interval were generated using median of medians. Results: A total of 40 studies reported time intervals for axi-cel (n=30), tisa-cel (n=13), and/or liso-cel (n=4) in r/r LBCL. Studies were not mutually exclusive by CAR T-cell product; however, time intervals were evaluated separately by product. V2Vt was the most reported interval. 31 studies reported V2Vt for axi-cel (n=22), tisa-cel (n=10), and/or liso-cel (n=3). Across all studies, axi-cel had the shortest median V2Vt (30.4 days vs 48.4 days for tisa-cel and 35.9 days for liso-cel; Table). Compared with real-world settings, median V2Vt was shorter in clinical trials for axi-cel (25.5 days vs 30.9 days) but not for tisa-cel (52.0 days vs 48.0 days). Liso-cel was only evaluable in clinical trials, where median V2Vt (35.9 days) was longer vs axi-cel in either clinical trial or real-world settings, except in Europe-only studies (38.0 days). Median V2Vt was shorter in US-only vs Europe-only studies for axi-cel (27.0 days vs 38.0 days) and tisa-cel (42.7 days vs 50.5 days). Prognostic value of time intervals for CAR T-cell therapy with respect to clinical outcomes was evaluated in 8 studies. Meta-analysis was not feasible due to data parameterization; however, one study noted an association between longer V2Vt and reduced effectiveness (Locke et al. ASH 2022; Poster #3345). Summary/Conclusion: In this meta-analysis of approved CAR T-cell products in r/r LBCL, axi-cel consistently had the shortest V2Vt compared with other products in clinical trial or real-world settings. Further evaluation of the factors impacting V2Vt, and their association with efficacy and other clinical outcomes, are warranted.Keywords: Systematic review, Cancer immunotherapy, CAR-T, B cell lymphoma
PB2571: FACTORS INFLUENCING POOR PROGNOSIS OF PATIENTS WITH HEMOPHAGOCYTE DETECTED BY BONE MARROW SMEAR AND CONSTRUCTION OF RISK PREDICTION MODEL
Authors: Ran Longrong, Peng Yu, Fu Huihui, Yang Zailin
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Hemophagocyte is a kind of special macrophage that engulfs living blood cells, mainly including nuclear red cells, red blood cells, neutrophils, platelets, lymphocytes, monocytes and so on. Hemophagocytosis can be found in bone marrow smears of patients with hemophagocytosis syndrome (HPS), infection, transfusion, bone injury, hemophagocytosis, autoimmune diseases, etc. As a quick and simple examination, the presence of hemophage in bone marrow smear is often the first indicator for detection of HPS, which is a very important indicator for timely detection of HLH. However, the etiology of hemocytosis in bone marrow is complex and the condition is changeable. The influence of hemocytosis on the prognosis of patients is still unclear, and there is a lack of unified prognostic evaluation and diagnosis and treatment standards, which brings challenges to diagnosis and treatment. Aims: The objective of this study was to analyze the factors influencing the prognosis of patients with hemophagocytosis found on bone marrow smears and to develop a new simple histogram model to evaluate the disease prognosis of patients with hemophagosis found on bone marrow smears. Methods: 84 patients with hemophagocytosis detected in bone marrow smears treated in our hospital from April 2017 to November 2021 were collected, their clinical data were analyzed, and the survival of patients were followed up. Through univariate and multivariate analysis, the related factors affecting the prognosis of patients were found. The prognosis evaluation model of patients with hemophagocytosis found in bone marrow smear was established by using the nomogram model. Results: Among the 84 patients, 35 met the diagnostic criteria for hemophagocytic syndrome and 49 did not, including 62 patients with fever, 34 patients with splenomegilia, 55 patients with hemocytopenia of series 2 and above, and 42 patients with elevated serum ferritin. Single-factor analysis by Lasso model showed that gender, fever, hepatomegaly, splenomegaly, cause, TBIL, UA, Fg, sCD25 and APTT all affected the prognosis of patients. Multivariate analysis showed that gender, splenomegaly, sCD25, UA and APTT could be independent risk factors for the prognosis of patients with hemophagocytic smears found in bone marrow. A prognosis evaluation system was established by means of nomogram model. Survival curve analysis showed that gender and etiology of patients could significantly affect the prognosis of patients. Summary/Conclusion: For the patients with detected hemophagocytophage, the prognosis of the patients can be analyzed through the analysis of the gender, splenomegaly, sCD25, UA and APTT related indicators, and the situation of the patients can be evaluated in a more comprehensive way to provide evidence for clinical treatment. Keywords: Hemophagocytic Lymphohistiocytosis (HLH), Prognosis
PB2651: A COMPARISON OF TIME TO TREATMENT WITH PROTHROMBIN COMPLEX CONCENTRATE: REMOTE OR POINT OF CARE STORAGE OF PCC
Authors: Samantha Bonney, Craig Rimmer, Ken Graham
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Prothrombin complex concentrate (PCC) is the recommended treatment for major bleeding in patients taking oral anticoagulants such as warfarin, apixaban, edoxaban and dabigatran. Its effectiveness is dependent on timely administration. Delays to treatment beyond one hour are common and adversely affect outcome. PCC is stored at room temperature, sometimes at point of care and sometimes remote from POC in the pathology department or hospital pharmacy. Current recommendations are that PCC should be stored at point of care (POC) with the aim of reducing delays caused by remote storage. Aims: The objectives of the present study were to investigate whether POC storage of PCC reduced delays to treatment in eligible patient Methods:Study Type A retrospective analysis of prospectively gathered information. Patients Adult patients treated with PCC in the Emergency Department (ED) of a general hospital in the UK from March 2021 to February 2023. Intervention Reconfigured the clinical pathway in March 2022 from laboratory issue of PCC on a named patient basis to storage at point of care (automated medicines dispensing system) in the ED. Comparison of outcomes, lab issue PCC (LAB) versus POC PCC: 1. Length of time between decision to give PCC and PCC administration 2. How many patients received PCC withing the recommended 1 hour from decision to treat Results: - Pre-Emergency Department Stock Post-Emergency Department Stock Number of patients issued PCC 20 (13 female) 34 (9 female) Mean age 79.4 years (range 60-99) 81.3 years (range 63- 92) Warfarin or DOAC 12 Warfarin 6 Apixaban1 not on anticoagulants1 on clexane 21 warfarin, 13 on DOAC (8 Apixaban, 4 Edoxaban, 1 Rivaroxaban) Mean time from PCC decision to administration (in ICH and actively bleeding patients, not surgical patients) 3.0 hours (range 1 hour 5 mins -5 hours 35 mins) 2.4 hours (range 12 mins- 7 hours 49 mins) PCC given within an hour of decision? 0/20 10/34 Summary/Conclusion No patients received PCC within an hour of the decision to give in the LAB compared with 29% of in the POC group. The time from decision to administration was also lower in the POC group (3 hours LAB Vs 2.4 hours POC). Keywords: Warfarin, Blood coagulation, Anticoagulants, Bleeding
PB2560: LYSOSOMAL STORAGE DISEASES: GUACHER’S DISEASE AND NIEMANPICK ‘S DISEASES: STUDY OF CLINICAL, CYTOLOGICAL AND ENZYMATIC ASPECTS
Authors: Lina Mohamed, Wided Moatemri, Amous Salma, Seif Ncibi, Haifa Hafsa, Nejia Braham Jmili, Haifa Regaieg, Kmira Zahra, Abderrahim Khelif
Journal: HemaSphere (2023)

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Lysosomal storage diseases (LSD) comprise a large group of rare inherited disorders (1 in every 7000 births) more than 40 LSD are known and classified based on biological and clinical suspects such as Gaucher ‘s disease and Nieman pick’s disease. These are lysosomal overload diseases characterized by a deficiency in β-glucocerebrosidase (BGS) responsible for a multisystem disease with varied clinical symptoms. Aims: The aim of this study was to study the concordance between the cytological aspect in the myelogram and the enzymatic essay. Methods: This is a retrospective descriptive study conducted in the hematology laboratory and biochemistry laboratory in collaboration with clinical hematology service at Farhat Hached Hospital in Sousse Tunisia. The patients included were those who presented with suspicion of having Gaucher ‘s disease or Nieman Pick ‘s disease between January 2013 and December 2022. Results: Our study included 28 patients in total. The median age was 22 years (range 1 and 52 years). The sex ratio (M/F) was 2.1. The circumstances of discovery were dominated by hepatosplenomegaly in 71.4 % of cases. A family history was also noted in 42% of cases. The cytopenia on the haemogram showed anaemia in 67.9% of cases, isolated in 15% of cases. A bicytopenia was observed in 85% of cases, dominated by the association of anaemia with thrombopenia in 81%. Myelogram showed the presence of Niemann Pick cells in 35% of cases while Gaucher cells were present in 53% of cases. The enzymatic assay was done for only 7 patients (Confirming the diagnosis in 4 cases). The median of BGS activity assay was 1.14 µkat/Kg of protein. The hexosaminidases assay was normal (300-850 µkat/Kg of protein) in 95 % of cases. the ratio BGS + taurocholic acid/ hexosaminidase was under the normal rage (0.83-1.45) in 70% of cases with a median of 0.5 (*100). Summary/Conclusion: The laboratory diagnosis of Gaucher’S disease and Niemann Pick ‘s disease should always be based on the enzymatic assay of BGS activity but also we can’t neglige the importance of the cytological aspect with the detection of storage cells in the myelogram. Keywords: Gaucher disease, Lysosomal storage disease
PB2537: PREDICTORS OF BACTERIAL INFECTION AMONG TRANSFUSION-DEPENDENT THALASSEMIA PATIENTS IN A TERTIARY GOVERNMENT HOSPITAL IN THE PHILIPPINES
Authors: Angelica Kristine Baylon, Hanisah Ana Danguilan, MA. Liza Naranjo
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: For the average Filipino child living with thalassemia, the definitive cure for the disease remains to be out of reach. Thus, healthcare workers are challenged to make the most of what is available to arrest the inevitable deterioration that transfusion-dependent thalassemia (TDT) patients face without definitive cure. Since it is known that bacterial infection is common among TDT patients, identifying which factors can predict bacterial infection can provide the healthcare team with a powerful tool to intervene early and take necessary action. Aims: The aim of this study was to determine the predictors of bacterial infection among TDT patients. Methods: Charts of all TDT patients admitted within 15 years were reviewed. Predictors of bacterial infection were identified using univariate and multivariate statistics. Chi-square test and logistic regression were used in the univariate analysis, and multiple logistic regression for multivariate analysis. Results: 141 patients were included. The prevalence of any bacterial infection was 51%. The most common types of infection were pneumonia (35%), skin infection (11%), and sepsis (9%). Patients with bacterial infection had a longer history of thalassemia and more frequent use of Deferiprone. History of splenectomy, vaccination status, and serum ferritin levels were not revealed to be significantly associated with bacterial infection status. The odds of a concurrent bacterial infection were 3.04 times as much in patients with >1 year of disease as in those with shorter duration, and 2.23 times as much in children with history of Deferipone use as in those without. Summary/Conclusion: There is a high prevalence of bacterial infection among TDT patients. Duration of disease and the use of Deferiprone were significantly associated with the occurrence of bacterial infection, and thus are the identified predictors thereof. History of splenectomy, vaccination status, and serum ferritin level were not significantly associated with occurrence of bacterial infection. Data from this research is recommended to be used as a starting point in the development of a scoring system to predict the occurrence of bacterial infection among TDT patients. Keywords: beta thalassemia, Thalassemia, Pediatric
PB2536: ACETAMINOPHEN AND CHLORPHENIRAMINE MALEATE PREMEDICATION IN PATIENTS WITH CHRONIC TRANSFUSION: A PROSPECTIVE, RANDOMIZED CONTROLLED TRIAL
Authors: Supanat Janyangam, Noppacharn Uaprasert
Journal: HemaSphere (2023)

Topic: 27. Thalassemias Background: Patients with chronic transfusion, especially transfusion dependent thalassemia, require regular red cell transfusion, which led to an increased susceptibility to transfusion reactions. Premedication with acetaminophen and/or chlorpheniramine maleate (CPM) is a common practice in Thailand despite the lack of clear benefits in the prevention of transfusion reactions. Aims: To evaluate the efficacy of acetaminophen and CPM as premedication in the prevention of febrile non-hemolytic transfusion reaction (FNHTR) and allergic transfusion reaction before leucocyte-poor red cells (LPRC). Methods: A prospective, randomized controlled trial was conducted in chronically transfused patients aged ≥18 years. We randomly assigned patients to one of two arms, in which patients will receive oral acetaminophen and intravenous CPM or placebo (calcium carbonate and normal saline) before LPRC transfusion. The primary end point was a combined incidence of FNHTR and allergic transfusion reaction in patients receiving oral acetaminophen and intravenous CPM compared to those with placebo. This trial was registered at Thai Clinical Trial Registry Study (TCTR20221011002). Results: A total of 94 patients were recruited into the study. Forty-six patients were assigned to the premedication arm, while 48 patients were assigned to the placebo arm. The incidence of FNHTR and allergic transfusion reaction in the premedication arm and the placebo arm was 0% and 2.1%, respectively (P value = 1.00). FNHTR occurred on 1 in the placebo arm. None of them had an allergic transfusion reaction. There were no adverse events with any medication. Summary/Conclusion: The incidence of FNHTR or allergic transfusion reaction is very low in patients with chronic transfusion with LPRC. Premedication with oral acetaminophen and intravenous CPM prior to LPRC transfusion did not have benefits in preventing very low transfusion events. Therefore, acetaminophen and CPM could be safely omitted in chronic transfused patients without a history of severe transfusion reactions. Keywords: Fever, Blood transfusion, Thalassemia
PB2503: MODULATION OF ERYTHROCYTE FUNCTION BY ENDOTHELIN-1
Authors: Lyzes Rosa Teixeira-Alves, Camila Cristina Guimarães-Nobre, Evelyn Mendonça Reis, Leandro Miranda-Alves, Clemilson Berto-Junior
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Endothelin-1 (ET-1) is a 21 amino acid residue peptide that has been described as a hormone produced only by endothelial cells. It is now clear that ET-1, in addition to playing important roles in vascular tone, is also responsible for mediate actions in other tissues and manly in disease states. Since it is a component derived from endothelial cells and sensitive to injury, ET-1 is found at high levels in plasma of patients with sickle cell disease (SCD). SCD is characterized by the presence of a mutated hemoglobin called hemoglobin S (HbS), which when deoxygenated, polymerizes, leading to sickle-shaped erythrocytes, vasooclusive events, decreased erythrocyte deformability, eryptosis, and enhanced adherence to endothelium. Aims: The present study used ex vivo experiments to asses the effects of ET-1, and bosentan (dual ET-1 receptors antagonist) on sickle erythrocytes HbS polymerization, deformability, adherence to thrombospondin, and eryptosis. Also, we aimed to determine which receptor is involved in these actions. Methods: Blood from SCD patients was harvested and washed 3 times with PBS and the buffy coat discarded. After last wash, packed erythrocytes were used. A polymerization assay was performed by adding ET-1 (1, 20 and 50 pg/mL), bosentan (100 nM), BQ-788 (1 uM) and BQ-3020 (1 uM), packed erythrocytes and sodium metabisulfite to a 96-well plate and readings performed for 30 minutes every minute. Static adhesion was also performed with packed erythrocytes, same ET-1 and bosentan concentration by placing them on 96-well plates; after one-hour incubation, wells were washed 3 times with PBS and remaining erythrocytes were lysed for quantification. Deformability was assessed by incubating packed erythrocytes with the same ET-1 and bosentan concentration and placing them on top of a Sephacryl S-500 column to separate deformable from non-deformable cells by centrifugation. Annexin V binding was performed in SCD erythrocytes samples adding ET-1, bosentan, with commercial kits. Results: ET-1 increased HbS polymerization in all concentrations used, being this effect inhibited by bosentan. Also, use of specific ETB agonists and antagonists demonstrated that this HbS polymerization enhancer effect promoted by ET-1 is mediated by ETB. ET-1 also decreased erythrocytes’ deformability, being this effect also blunted by bosentan. Regarding adhesion, ET-1 decreased adhesion to thrombospondin with bosentan enhancing this effect. Measured eryptosis also showed decreased annexin V binding induced by endothelin with bosentan inhibiting this effect. Summary/Conclusion: In conclusion, we note that high abundant ET-1 levels in patients with SCD is harmful for most of erythrocytes function with bosentan reversing these effects and that this ET-1 effect on HbS polymerization is mediated by the ETB receptor.Keywords: Sickle cell adhesion, Sickle cell disease, Apoptosis
PB2521: STUDY OF HEMOGLOBIN S-OMAN TRAIT: NEW INSIGHTS
Authors: Nouh Al-Mahrouqi, Maha Al Awadi, Aisha Al Hosni, Murtadha Al Khabori, Abdul Hakim Al Rawas, Mohammed Al Rawahi, Ameera Al-Rahbi, Shahina Daar, Yasser Wali
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Hemoglobin SOman is a sickle hemoglobinopathy that results from two mutations in Beta globin chain, at position 6 and 121; (B6 Glu>>>Val) and (B121 Glu>>>Lys). At cellular level, Hb SOman has a super-sickling tendency more than the classic Hb S, due to the additional mutation (B121 Glu>>>Lys). Previously, it has been reported in only 5 carriers that the disease has variable clinical features based on the presence of alpha thalassemia trait and the expression of Hb SOman level. Aims: Our aim is to study the disease clinical and hematological characteristics, focusing on phenotype/genotype correlation and association with alpha thalassemia. Methods: This is a cross-sectional descriptive study of 69 patients confirmed to have Hb SOman trait. 60 patients were tested for alpha thalassemia and their clinical and hematological profile were analyzed. Results: A total number of Hb SOman trait patients was 69. The mean age was 27.5 years; males and females were affected equally (Table 1). Alpha thalassemia trait (_α/_α) was co-inherited in 73% of Hb SOman patients, 20% were carriers (_α/ αα) and 7% were normal genotype (αα/ αα). There was no significant clinical course and hematological characteristics differences between patients of HbSOman with alpha thalassemia trait or without alpha thalassemia. However, HbSOman level was found to be the most specific factor associated with increased clinical severity (P<≤ 0.001). Summary/Conclusion: Hb SOman trait phenotype can present with severe manifestation similar to SCD and co-inheritance of alpha thalassemia trait does not affect its severity. Hb SOman level correlates well with disease severity. Table I: Demographic, clinical and laboratory data of all patients n=69 - Clinical profile Mean SEM Gender (n) 34 Male; 35 Female Age (years) 27.5 3.05 Wilayat Nakhal n (%) 35(50.7%) Bahla n (%) 24(34.7%) Sumail n (%) 4(5.7%) Alaamerat n (%) 6(8.6%) Severity (%) 52 Mild; 48 severe HbS-Oman (%) 16.69 0.54 HbF (%) 4.16 0.30 HbA2 (%) 3.99 0.08 Hb (g/l) 11.64 0.26 Platelets (x 103/uL) 275 12.92 ANC (x 103/uL) 3.08 0.70 Vaso-occlusive crisis(VOC) n (%) 37(53%) Simple Blood transfusion n (%) 13(19.9%) Exchange transfusion n (%) 7(10.8%) ACS n (%) 11(17.2%) Stroke n (%) 3(4.7%) Splenic sequestration n (%) 4(6.2%) Gallstones n (%) 1(1.5%) Avascular necrosis n (%) 5(7.7%) Osteomyelitis n (%) 1(1.5%) Iron overload/chelation therapy n (%) 1(1.5%) Hydroxyurea n (%) 11(17.2%) Surgeries (splenectomy/cholecystectomy/joint replacement) n (%) 2(3%) Bone Marrow Transplantation(BMT) 0(0%) Death 0(0%) Keywords: Sickle cell